The shape of the dose-response curve to histamine in asthmatic and normal subjects

Abstract

In order to determine the shape of the dose-response curves of the human airways to bronchial challenge, changes in forced expiratory volume in one second (FEV1) after inhaled histamine were measured in 8 current asthmatic, 2 mildly asthmatic, and 10 normal subjects. The challenges were continued until a plateau was reached (in all the normal and in the 2 mildly asthmatic subjects), or the FEV1 had fallen by 60%. A sigmoidal equation was fitted to the data points to obtain values for alpha (the position constant) and beta (the slope constant). All the normal and the 2 mildly asthmatic subjects reached a plateau value for fall in FEV1. Current asthmatics were differentiated from normal and mildly asthmatic subjects by the failure to reach a plateau at a 60% fall in FEV1 by higher values for alpha (greater sensitivity to histamine) and by higher values for beta. Ipratropium bromide (an atropinelike drug), in doses that completely inhibited the effects of methacholine, caused no change in the shape or position of the curves in normal or asthmatic subjects. It is concluded that the nature of the airway response to histamine is different in asthmatic from that in normal subjects. It is possible that asthmatics lack a normal mechanism that inhibits severe airway narrowing during histamine challenge.